Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

  • Jan BooijEmail author
  • Paul Kemp
Review Article



[123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([123I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [123I]FP-CIT SPECT scans.


Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [123I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [123I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [123I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [123I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient’s care and taking into account the pros and cons of doing so.


[123I]FP-CIT SPECT Dopamine transporter Drugs Withdrawal Effects 



The authors would like to thank Remco JJ Knol (MD) for the production of Fig. 1. The authors declare no conflict of interest.


  1. 1.
    Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 1973;20:415–55.PubMedGoogle Scholar
  2. 2.
    Kaufman MJ, Madras BK. Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson’s-diseased striatum. Synapse 1991;9:43–9.PubMedGoogle Scholar
  3. 3.
    Garnett ES, Firnau G, Nahmias C. Dopamine visualised in the basal ganglia of living man. Nature 1983;305:137–8.PubMedGoogle Scholar
  4. 4.
    Frey KA, Koeppe RA, Kilbourn MR, Vander Borght TM, Albin RL, Gilman S, et al. Presynaptic monoaminergic vesicles in Parkinson’s disease and normal aging. Ann Neurol 1996;40:873–84.PubMedGoogle Scholar
  5. 5.
    Booij J, Tissingh G, Boer GJ, Speelman JD, Stoof JC, Janssen AG, et al. [123I]FP-CIT SPECT shows a pronounced decline of striatal dopamine transporter labelling in early and advanced Parkinson’s disease. J Neurol Neurosurg Psychiatry 1997;62:133–40.PubMedCrossRefGoogle Scholar
  6. 6.
    Innis RB, Seibyl JP, Scanley BE, Laruelle M, Abi-Dargham A, Wallace E, et al. Single photon emission computed tomographic imaging demonstrates loss of striatal dopamine transporters in Parkinson disease. Proc Natl Acad Sci USA 1993;90:11965–9.PubMedGoogle Scholar
  7. 7.
    Halldin C, Erixon-Lindroth N, Pauli S, Chou YH, Okubo Y, Karlsson P, et al. [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain. Eur J Nucl Med Mol Imaging 2003;30:1220–30.PubMedGoogle Scholar
  8. 8.
    Kung HF, Kim HJ, Kung MP, Meegalla SK, Plossl K, Lee HK. Imaging of dopamine transporters in humans with technetium-99m TRODAT-1. Eur J Nucl Med 1996;23:1527–30.PubMedGoogle Scholar
  9. 9.
    Rinne JO, Laihinen A, Nagren K, Ruottinen H, Ruotsalainen U, Rinne UK. PET examination of the monoamine transporter with [11C]β-CIT and [11C]β-CFT in early Parkinson’s disease. Synapse 1995;21:97–103.PubMedGoogle Scholar
  10. 10.
    Farde L, Ehrin E, Eriksson L, Greitz T, Hall H, Hedström CG, et al. Substituted benzamides as ligands for visualization of dopamine receptor binding in the human brain by positron emission tomography. Proc Natl Acad Sci USA 1985;82:3863–7.PubMedGoogle Scholar
  11. 11.
    Kung HF, Alavi A, Chang W, Kung MP, Keyes JW Jr, Velchik MG, et al. In vivo SPECT imaging of CNS D-2 dopamine receptors: initial studies with iodine-123-IBZM in humans. J Nucl Med 1990;31:573–9.PubMedGoogle Scholar
  12. 12.
    Mukherjee J, Christian BT, Dunigan KA, Shi B, Narayanan TK, Satter M, et al. Brain imaging of 18F-fallypride in normal volunteers: blood analysis, distribution, test–retest studies, and preliminary assessment of sensitivity to aging effects on dopamine D-2/D-3 receptors. Synapse 2002;46:170–88.PubMedGoogle Scholar
  13. 13.
    Booij J, Tissingh G, Winogrodzka A, van Royen EA. Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism [review]. Eur J Nucl Med 1999;26:171–82.PubMedGoogle Scholar
  14. 14.
    Marshall V, Grosset D. Role of dopamine transporter imaging in routine clinical practice [review]. Mov Disord 2003;18:1415–23.PubMedGoogle Scholar
  15. 15.
    Ponsen MM, Stoffers D, Booij J, van Eck-Smit BL, Wolters ECh, Berendse HW. Idiopathic hyposmia as a preclinical sign of Parkinson’s disease. Ann Neurol 2004;56:173–81.PubMedGoogle Scholar
  16. 16.
    Stiasny-Kolster K, Doerr Y, Moller JC, Hoffken H, Behr TM, Oertel WH, et al. Combination of ‘idiopathic’ REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 2005;128:126–37.PubMedGoogle Scholar
  17. 17.
    O’Brien JT, Colloby S, Fenwick J, Williams ED, Firbank M, Burn D, et al. Dopamine transporter loss visualized with FP-CIT SPECT in the differential diagnosis of dementia with Lewy bodies. Arch Neurol 2004;61:919–25.PubMedGoogle Scholar
  18. 18.
    Walker Z, Costa DC, Walker RW, Shaw K, Gacinovic S, Stevens T, et al. Differentiation of dementia with Lewy bodies from Alzheimer’s disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg Psychiatry 2002;73:134–40.PubMedGoogle Scholar
  19. 19.
    McKeith I, O’Brien J, Walker Z, Tatsch K, Booij J, Darcourt J, et al. Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre study. Lancet Neurol 2007;6:305–13.PubMedGoogle Scholar
  20. 20.
    Ishikawa T, Dhawan V, Kazumata K, Chaly T, Mandel F, Neumeyer J, et al. Comparative nigrostriatal dopaminergic imaging with iodine-123-beta-CIT-FP/SPECT and fluorine-18-FDOPA/PET. J Nucl Med 1996;37:1760–5.PubMedGoogle Scholar
  21. 21.
    Booij J, Busemann Sokole E, Stabin MG, Janssen AG, de Bruin K, van Royen EA. Human biodistribution and dosimetry of [123I]FP-CIT: a potent radioligand for imaging of dopamine transporters. Eur J Nucl Med 1998;25:24–30. Erratum in: Eur J Nucl Med 1998;25:458.PubMedGoogle Scholar
  22. 22.
    Booij J, Hemelaar TG, Speelman JD, de Bruin K, Janssen AG, van Royen EA. One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson’s disease by [123I]FPCIT SPECT. J Nucl Med 1999;40:753–61.PubMedGoogle Scholar
  23. 23.
    Benamer TS, Patterson J, Grosset DG, Booij J, de Bruin K, van Royen E, et al. Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000;15:503–10.PubMedGoogle Scholar
  24. 24.
    Catafau AM, Tolosa E, [123I]FP-CIT Clinically Uncertain Parkinsonian Syndromes Study Group. Impact of dopamine transporter SPECT using 123I-Ioflupane on diagnosis and management of patients with clinically uncertain Parkinsonian syndromes. Mov Disord 2004;19:1175–82.PubMedGoogle Scholar
  25. 25.
    Varrone A, Pellecchia MT, Amboni M, Sansone V, Salvatore E, Ghezzi D, et al. Imaging of dopaminergic dysfunction with [123I]FP-CIT SPECT in early-onset parkin disease. Neurology 2004;63:2097–103.PubMedGoogle Scholar
  26. 26.
    Andringa G, Drukarch B, Bol JGJM, de Bruin K, Sorman K, Habraken JB, et al. Pinhole SPECT imaging of dopamine transporters correlates with dopamine transporter immunohistochemical analysis in the MPTP mouse model of Parkinson’s disease. Neuroimage 2005;26:1150–8.PubMedGoogle Scholar
  27. 27.
    Salvatore E, Varrone A, Sansone V, Nolano M, Bruni AC, De Rosa A, et al. Characterization of nigrostriatal dysfunction in spinocerebellar ataxia 17. Mov Disord 2006;21:872–5.PubMedGoogle Scholar
  28. 28.
    Spiegel J, Hellwig D, Mollers MO, Behnke S, Jost W, Fassbender K, et al. Transcranial sonography and [123I]FP-CIT SPECT disclose complementary aspects of Parkinson’s disease. Brain 2006;129:1188–93.PubMedGoogle Scholar
  29. 29.
    Lavalaye J, Linszen DH, Booij J, Dingemans PM, Reneman L, Habraken JB, et al. Dopamine transporter density in young patients with schizophrenia assessed with [123I]FP-CIT SPECT. Schizophr Res 2001;47:59–67.PubMedGoogle Scholar
  30. 30.
    Neumeyer JL, Wang S, Gao Y, Milius RA, Kula NS, Campbell A, et al. N-ω-fluoroalkyl analogs of (1R)-2β-carbomethoxy-3β-(4-iodophenyl)-tropane (β-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. J Med Chem 1994;37:1558–61.PubMedGoogle Scholar
  31. 31.
    Scheffel U, Lever JR, Abraham P, Parham KR, Mathews WB, Kopajtic T, et al. N-substituted phenyltropanes as in vivo binding ligands for rapid imaging studies of the dopamine transporter. Synapse 1997;25:345–9.PubMedGoogle Scholar
  32. 32.
    Laruelle M, Baldwin RM, Malison RT, Zea-Ponce Y, Zoghbi SS, al-Tikriti MS, et al. SPECT imaging of dopamine and serotonin transporters with [123I]β-CIT: pharmacological characterization of brain uptake in nonhuman primates. Synapse 1993;13:295–309.PubMedGoogle Scholar
  33. 33.
    Booij J, Andringa G, Rijks LJ, Vermeulen RJ, De Bruin K, Boer GJ, et al. [123I]FP-CIT binds to the dopamine transporter as assessed by biodistribution studies in rats and SPECT studies in MPTP-lesioned monkeys. Synapse 1997;27:183–90.PubMedGoogle Scholar
  34. 34.
    Vles JS, Feron FJ, Hendriksen JG, Jolles J, van Kroonenburgh MJ, Weber WE. Methylphenidate down-regulates the dopamine receptor and transporter system in children with attention deficit hyperkinetic disorder (ADHD). Neuropediatrics 2003;34:77–80.PubMedGoogle Scholar
  35. 35.
    Ginovart N, Wilson AA, Houle S, Kapur S. Amphetamine pretreatment induces a change in both D2-Receptor density and apparent affinity: a [11C]raclopride positron emission tomography study in cats. Biol Psychiatry 2004;55:1188–94.PubMedGoogle Scholar
  36. 36.
    Saunders C, Ferrer JV, Shi L, Chen J, Merrill G, Lamb ME, et al. Amphetamine-induced loss of human dopamine transporter activity: An internalization-dependent and cocaine-sensitive mechanism. Proc Natl Acad Sci USA 2000;97:6850–5.PubMedGoogle Scholar
  37. 37.
    Byas-Smith M, Votaw J, Hua J, Voll R, Martarello L, Levey AI, et al. Phenylephrine and norepinephrine increase dopamine transporter ligand binding in striatum. Mol Imaging Biol 2003;5:217–26.PubMedGoogle Scholar
  38. 38.
    Kish SJ, Furukawa Y, Chang LJ, Tong J, Ginovart N, Wilson A, et al. Regional distribution of serotonin transporter protein in postmortem human brain. Is the cerebellum a SERT-free brain region? Nucl Med Biol 2005;32:123–8.PubMedGoogle Scholar
  39. 39.
    Reneman L, Booij J, Lavalaye J, de Bruin K, Reitsma JB, Gunning B, et al. Use of amphetamine by recreational users of ecstasy (MDMA) is associated with reduced striatal dopamine transporter densities: a [123I]β-CIT SPECT study—preliminary report. Psychopharmacology (Berl) 2002;159:335–40.Google Scholar
  40. 40.
    Kahlig KM, Galli A. Regulation of dopamine transporter function and plasma membrane expression by dopamine, amphetamine, and cocaine [review]. Eur J Pharmacol 2003;479:153–8.PubMedGoogle Scholar
  41. 41.
    Qian Y, Galli A, Ramamoorthy S, Risso S, DeFelice LJ, Blakely RD. Protein kinase C activation regulates human serotonin transporters in HEK-293 cells via altered cell surface expression. J Neurosci 1997;17:45–7.PubMedGoogle Scholar
  42. 42.
    Foster JD, Cervinski MA, Gorentla BK, Vaughan RA. Regulation of the dopamine transporter by phosphorylation. Handb Exp Pharmacol 2006;175:197–214.PubMedCrossRefGoogle Scholar
  43. 43.
    Foster JD, Pananusorn B, Vaughan RA. Dopamine transporters are phosphorylated on N-terminal serines in rat striatum. J Biol Chem 2002;277:25178–86.PubMedGoogle Scholar
  44. 44.
    Ramamoorthy S, Blakely RD. Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants. Science 1999;285:763–6.PubMedGoogle Scholar
  45. 45.
    Melikian HE, Buckley KM. Membrane trafficking regulates the activity of the human dopamine transporter. J Neurosci 1999;19:7699–710.PubMedGoogle Scholar
  46. 46.
    Jayanthi LD, Ramamoorthy S. Regulation of monoamine transporters: influence of psychostimulants and therapeutic antidepressants [review]. AAPS J 2005;7:E728–38.PubMedGoogle Scholar
  47. 47.
    Gulley JM, Zahniser NR. Rapid regulation of dopamine transporter function by substrates, blockers and presynaptic receptor ligands. Eur J Pharmacol 2003;479:139–52.PubMedGoogle Scholar
  48. 48.
    Inaba T. Cocaine: pharmacokinetics and biotransformation in man. Can J Physiol Pharmacol 1989;67:1154–7.PubMedGoogle Scholar
  49. 49.
    Brandenberger H, Maes RAA, editors. Analytical toxicology for clinical, forensic, and pharmacuetical chemists. Berlin: Walter de Gruyter; 1977. p. 665–72.Google Scholar
  50. 50.
    Chaly T, Dhawan V, Kazumata K, Antonini A, Margouleff C, Dahl JR, et al. Radiosynthesis of [18F] N-3-fluoropropyl-2-β-carbomethoxy-3-β-(4-iodophenyl) nortropane and the first human study with positron emission tomography. Nucl Med Biol 1996;23:999–1004.PubMedGoogle Scholar
  51. 51.
    Bergström KA, Halldin C, Lundkvist C, Swahn C-G, Åkerman KK, Kuikka JT, et al. Characterization of C-11 or I-123 labelled β-CIT-FP and β-CIT-FE metabolism measured in monkey and human plasma. Identification of two labeled metabolites with HPLC. Hum Psychopharmacol 1996;11:483–90.Google Scholar
  52. 52.
    Kula NS, Baldessarini RJ, Tarazi FI, Fisser R, Wang S, Trometer J, et al. [3H]β-CIT: a radioligand for dopamine transporters in rat brain tissue. Eur J Pharmacol 1999;385:291–4.PubMedGoogle Scholar
  53. 53.
    Pellinen P, Honkakoski P, Stenback F. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur J Pharmacol 1994;270:35–43.PubMedGoogle Scholar
  54. 54.
    Yaqub M, Boellaard R, van Berckel BN, Ponsen MM, Lubberink M, Windhorst AD, et al. Quantification of dopamine transporter binding using [18F]FP-β-CIT and positron emission tomography. J Cereb Blood Flow Metab 2007;27:1397–406.PubMedGoogle Scholar
  55. 55.
    Lammertsma AA, Bench CJ, Price GW, Cremer JE, Luthra SK, Turton D, et al. Measurement of cerebral monoamine oxidase B activity using L-[11C]deprenyl and dynamic positron emission tomography. J Cereb Blood Flow Metab 1991;11:545–56.PubMedGoogle Scholar
  56. 56.
    Gunduz H, Wu H, Ashtari M, Bogerts B, Crandall D, Robinson DG, et al. Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects. Biol Psychiatry 2002;51:801–8.PubMedGoogle Scholar
  57. 57.
    Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D’Souza DC, Krystal J, et al. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT. Biol Psychiatry 2000;47:371–9.PubMedGoogle Scholar
  58. 58.
    Lavalaye J, Booij J, Reneman L, Habraken JB, van Royen EA. Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers. Eur J Nucl Med 2000;27:867–9.PubMedGoogle Scholar
  59. 59.
    Booij J, Habraken JB, Bergmans P, Tissingh G, Winogrodzka A, Wolters EC, et al. Imaging of dopamine transporters with iodine-123-FP-CIT SPECT in healthy controls and patients with Parkinson’s disease. J Nucl Med 1998;39:1879–84.PubMedGoogle Scholar
  60. 60.
    Qin Y, Ouyang Q, Pablo J, Mash DC. Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the human striatum. Neuroreport 2005;16:1489–93.PubMedGoogle Scholar
  61. 61.
    Malison RT, Best SE, van Dyck CH, McCance EF, Wallace EA, Laruelle M, et al. Elevated striatal dopamine transporters during acute cocaine abstinence as measured by [123I]β-CIT SPECT. Am J Psychiatry 1998;155:832–4.PubMedGoogle Scholar
  62. 62.
    Volkow ND, Wang GJ, Fischman MW, Foltin RW, Fowler JS, Abumrad NN, et al. Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature 1997;386:827–30.PubMedGoogle Scholar
  63. 63.
    Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, et al. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 2001;158:377–82.Google Scholar
  64. 64.
    Chou YH, Huang WS, Su TP, Lu RB, Wan FJ, Fu YK. Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: a SPECT study. Eur Neuropsychopharmacol 2007;17:46–52.PubMedGoogle Scholar
  65. 65.
    McCann UD, Wong DF, Yokoi F, Villemagne V, Dannals RF, Ricaurte GA. Reduced striatal dopamine transporter density in abstinent methamphetamine and methcathinone users: evidence from positron emission tomography studies with [11C]WIN-35,428. J Neurosci 1998;180:8417–22.Google Scholar
  66. 66.
    Volkow ND, Chang L, Wang GJ, Fowler JS, Franceschi D, Sedler M, et al. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci 2001;21:9414–8.PubMedGoogle Scholar
  67. 67.
    Sekine Y, Iyo M, Ouchi Y, Matsunaga T, Tsukada H, Okada H, et al. Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. Am J Psychiatry 2001;158:1206–14.PubMedGoogle Scholar
  68. 68.
    Spencer TJ, Biederman J, Ciccone PE, Madras BK, Dougherty DD, Bonab AA, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry 2006;163:387–95.PubMedGoogle Scholar
  69. 69.
    Gruber AJ, Pope HG. Ephedrine abuse among 36 female weightlifters. Am J Addict 1998;7:256–61.PubMedCrossRefGoogle Scholar
  70. 70.
    Alexander M, Rothman RB, Baumann MH, Endres CJ, Brasic JR, Wong DF. Noradrenergic and dopaminergic effects of (+)-amphetamine-like stimulants in the baboon Papio anubis. Synapse 2005;56:94–9.PubMedGoogle Scholar
  71. 71.
    Wee S, Ordway GA, Woolverton WL. Reinforcing effect of pseudoephedrine isomers and the mechanism of action. Eur J Pharmacol 2004;493:117–25.PubMedGoogle Scholar
  72. 72.
    Rothman RB, Vu N, Partilla JS, Roth BL, Hufeisen SJ, Compton-Toth BA, et al. In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. J Pharmacol Exp Ther 2003;307:138–45.PubMedGoogle Scholar
  73. 73.
    Rothman RB, Blough BE, Baumann MH. Dual dopamine-5-HT releasers: potential treatment agents for cocaine addiction [review]. Trends Pharmacol Sci 2006;27:612–8.PubMedGoogle Scholar
  74. 74.
    Mark EJ, Patalas ED, Chang HT, Evans RJ, Kessler SC. Fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl J Med 1997;337:602–6. Erratum in: N Engl J Med 1997;337:1483.PubMedGoogle Scholar
  75. 75.
    Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, et al. Valvular heart disease associated with fenfluramine–phentermine. N Engl J Med 1997;337:581–8. Erratum in: N Engl J Med 1997;337:1783.PubMedGoogle Scholar
  76. 76.
    Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med 2005;143:380–5.PubMedGoogle Scholar
  77. 77.
    Vaugeois JM, Bonnet JJ, Costentin J. In vivo labelling of the neuronal dopamine uptake complex in the mouse striatum by [3H]GBR 12783. Eur J Pharmacol 1992;210:77–84.PubMedGoogle Scholar
  78. 78.
    Giambalvo CT, Price LH. Effects of fenfluramine and antidepressants on protein kinase C activity in rat cortical synaptoneurosomes. Synapse 2003;50:212–22.PubMedGoogle Scholar
  79. 79.
    McCann UD, Seiden LS, Rubin LJ, Ricaurte GA. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine. A systematic review of the evidence. JAMA 1997;278:666–72.PubMedGoogle Scholar
  80. 80.
    Mignot E, Nishino S, Guilleminault C, Dement WC. Modafinil binds to the dopamine uptake carrier site with low affinity. Sleep 1994;17:436–7.PubMedGoogle Scholar
  81. 81.
    Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM. Dopaminergic role in stimulant-induced wakefulness. J Neurosci 2001;21:1787–94.PubMedGoogle Scholar
  82. 82.
    Madras BK, Xie Z, Lin Z, Jassen A, Panas H, Lynch L, et al. Modafinil occupies dopamine and norepinephrine transporters in vivo and modulates the transporters and trace amine activity in vitro. J Pharmacol Exp Ther 2006;319:561–9.PubMedGoogle Scholar
  83. 83.
    Malison RT, McCance E, Carpenter LL, Baldwin RM, Seibyl JP, Price LH, et al. [123I]β-CIT SPECT imaging of dopamine transporter availability after mazindol administration in human cocaine addicts. Psychopharmacology 1998;137:321–5.PubMedGoogle Scholar
  84. 84.
    Argyelan M, Szabo Z, Kanyo B, Tanacs A, Kovacs Z, Janka Z, et al. Dopamine transporter availability in medication free and in bupropion treated depression: a 99mTc-TRODAT-1 SPECT study. J Affect Disord 2005;89:115–23.PubMedGoogle Scholar
  85. 85.
    Meyer JH, Goulding VS, Wilson AA, Hussey D, Christensen BK, Houle S. Bupropion occupancy of the dopamine transporter is low during clinical treatment. Psychopharmacology 2002;163:102–5.PubMedGoogle Scholar
  86. 86.
    Learned-Coughlin SM, Bergstrom M, Savitcheva I, Ascher J, Schmith VD, Langstrom B. In vivo activity of bupropion at the human dopamine transporter as measured by positron emission tomography. Biol Psychiatry 2003;54:800–5.PubMedGoogle Scholar
  87. 87.
    Kugaya A, Seneca NM, Snyder PJ, Williams SA, Malison RT, Baldwin RM, et al. Changes in human in vivo serotonin and dopamine transporter availabilities during chronic antidepressant administration. Neuropsychopharmacology 2003;28:413–20.PubMedGoogle Scholar
  88. 88.
    Reneman L, Booij J, Lavalaye J, de Bruin K, Reitsma JB, Gunning B, et al. Use of amphetamine by recreational users of ecstasy (MDMA) is associated with reduced striatal dopamine transporter densities: a [123I]β-CIT SPECT study—preliminary report. Psychopharmacology (Berl) 2002;159:335–40.Google Scholar
  89. 89.
    de Win MM, Habraken JB, Reneman L, van den Brink W, den Heeten GJ, Booij J. Validation of [123I]β-CIT SPECT to assess serotonin transporters in vivo in humans: a double-blind, placebo-controlled, crossover study with the selective serotonin reuptake inhibitor citalopram. Neuropsychopharmacology 2005;30:996–1005.PubMedGoogle Scholar
  90. 90.
    Booij J, de Jong J, de Bruin K, Knol RJJ, de Win MM, van Eck-Smit BLF. Quantification of striatal dopamine transporters with [123I]FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy controls. J Nucl Med 2007;48:359–66.PubMedGoogle Scholar
  91. 91.
    Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry 2001;50:345–50.PubMedGoogle Scholar
  92. 92.
    Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997;340:249–58.PubMedGoogle Scholar
  93. 93.
    Scheffel U, Kim S, Cline EJ, Kuhar MJ. Occupancy of the serotonin transporter by fluoxetine, paroxetine, and sertraline: in vivo studies with [125I]RTI-55. Synapse 1994;16:263–8.PubMedGoogle Scholar
  94. 94.
    Inoue O, Kobayashi K, Hosoi R, Gee A. Opposing effects of clomipramine on [125I]RTI-55 and [3H]N-methylspiperone binding in mouse striatum: important role of other factors than endogenous dopamine? Synapse 1998;30:338–40.PubMedGoogle Scholar
  95. 95.
    Fujita M, Takatoku K, Matoba Y, Nishiura M, Kobayashi K, Inoue O, et al. Enhancement of [123I]β-CIT binding in the striatum with clomipramine: is there a serotonin–dopamine interaction? Eur J Nucl Med 1997;24:403–8.PubMedGoogle Scholar
  96. 96.
    Shang Y, Gibbs MA, Marek GJ, Stiger T, Burstein AH, Marek K, et al. Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a [123I]2β-carbomethoxy-3β-(4-iodophenyl)-tropane single photon emission computed tomography imaging study. J Clin Psychopharmacol 2007;27:71–5.PubMedGoogle Scholar
  97. 97.
    Volkow ND, Wang GJ, Fowler JS, Learned-Coughlin S, Yang J, Logan J, et al. The slow and long-lasting blockade of dopamine transporters in human brain induced by the new antidepressant drug radafaxine predict poor reinforcing effects. Biol Psychiatry 2005;57:640–6.PubMedGoogle Scholar
  98. 98.
    Chen F, Lawrence AJ. The effects of antidepressant treatment on serotonergic and dopaminergic systems in Fawn-Hooded rats: a quantitative autoradiography study. Brain Res 2003;976:22–9.PubMedGoogle Scholar
  99. 99.
    Thibaut F, Bonnet JJ, Vaugeois JM, Costentin J. Pharmacological modifications of dopamine transmission do not influence the striatal in vivo binding of [3H]mazindol or [3H]cocaine in mice. Neurosci Lett 1996;205:145–8.PubMedGoogle Scholar
  100. 100.
    Tatsumi M, Jansen K, Blakely RD, Richelson E. Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol 1999;368:277–83.PubMedGoogle Scholar
  101. 101.
    Basta-Kaim A, Budziszewska B, Jaworska-Feil LM, Tetich M, Kubera M, Leskiewicz M, et al. Antipsychotic drugs inhibit the human corticotropin-releasing-hormone gene promoter activity in neuro-2A cells—an involvement of protein kinases. Neuropsychopharmacology 2006;31:853–65.PubMedGoogle Scholar
  102. 102.
    Mateos JJ, Lomena F, Parellada E, Mireia F, Fernandez-Egea E, Pavia J, et al. Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait. Psychopharmacology (Berl) 2007;191:805–11.Google Scholar
  103. 103.
    Lavalaye J, Booij J, Reneman L, Habraken JB, van Royen EA. [123I]FP-CIT binding in rat brain after acute and sub-chronic administration of dopaminergic medication. Eur J Nucl Med 2000;27:346–9.PubMedGoogle Scholar
  104. 104.
    Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med 2004;351:2509–18.PubMedGoogle Scholar
  105. 105.
    Thomas AJ, Burn DJ, Rowan EN, Littlewood E, Newby J, Cousins D, et al. A comparison of the efficacy of donepezil in Parkinson’s disease with dementia and dementia with Lewy bodies. Int J Geriatr Psychiatry 2005;20:938–44.PubMedGoogle Scholar
  106. 106.
    Tsukada H, Nishiyama S, Ohba H, Sato K, Harada N, Kakiuchi T. Cholinergic neuronal modulations affect striatal dopamine transporter activity: PET studies in the conscious monkey brain. Synapse 2001;42:193–5.PubMedGoogle Scholar
  107. 107.
    Taylor J-P, Colloby SJ, McKeith IG, Burn DJ, Williams D, Patterson J, et al. Cholinesterase inhibitor use does not significantly influence the ability of 123I-FP-CIT imaging to distinguish AD from DLB. J Neurol Neurosurg Psychiatry 2007;78:1069–71PubMedGoogle Scholar
  108. 108.
    Kilbourn MR, Kemmerer ES, Desmond TJ, Sherman PS, Frey KA. Differential effects of scopolamine on in vivo binding of dopamine transporter and vesicular monoamine transporter radioligands in rat brain. Exp Neurol 2004;188:387–90.PubMedGoogle Scholar
  109. 109.
    Lees 2005. Alternatives to levodopa in the initial treatment of early Parkinson’s disease. Drugs Aging 2005;22:731–740.PubMedGoogle Scholar
  110. 110.
    Madras BK, Fahey MA, Goulet M, Lin Z, Bendor J, Goodrich C, et al. Dopamine transporter (DAT) inhibitors alleviate specific parkinsonian deficits in monkeys: association with DAT occupancy in vivo. J Pharmacol Exp Ther 2006;319:570–85.PubMedGoogle Scholar
  111. 111.
    Lees AJ. Drugs for Parkinson’s disease [review]. J Neurol Neurosurg Psychiatry 2002;73:607–10.PubMedGoogle Scholar
  112. 112.
    Winogrodzka A, Booij J, Wolters ECh. Disease-related and drug-induced changes in dopamine transporter expression might undermine the reliability of imaging studies of disease progression in Parkinson’s disease [review]. Parkinsonism Relat Disord 2005;11:475–84.PubMedGoogle Scholar
  113. 113.
    Schillaci O, Pierantozzi M, Filippi L, Manni C, Brusa L, Danieli R, et al. The effect of levodopa therapy on dopamine transporter SPECT imaging with 123I-FP-CIT in patients with Parkinson’s disease. Eur J Nucl Med Mol Imaging 2005;32:1452–6.PubMedGoogle Scholar
  114. 114.
    Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004;351:2498–508.PubMedGoogle Scholar
  115. 115.
    Innis RB, Marek KL, Sheff K, Zoghbi S, Castronuovo J, Feigin A, et al. Effect of treatment with L-dopa/carbidopa or L-selegiline on striatal dopamine transporter SPECT imaging with [123I]β-CIT. Mov Disord 1999;14:436–42.PubMedGoogle Scholar
  116. 116.
    Fowler JS, Volkow ND, Logan J, Franceschi D, Wang GJ, MacGregor R, et al. Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain. Life Sci 2001;68:2759–68.PubMedGoogle Scholar
  117. 117.
    Heinonen EH, Anttila MI, Lammintausta RA. Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites [review]. Clin Pharmacol Ther 1994;56:742–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Winogrodzka A, Bergmans P, Booij J, van Royen EA, Stoof JC, Wolters EC. [123I]β-CIT SPECT is a useful method for monitoring dopaminergic degeneration in early stage Parkinson’s disease. J Neurol Neurosurg Psychiatry 2003;74:294–8.PubMedGoogle Scholar
  119. 119.
    Ahlskog JE, Uitti RJ, O’Conor MK, Maraganore DM, Matsumoto JY, Stark KF, et al. The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson’s disease. Mov Disord 1999;14:940–6.PubMedGoogle Scholar
  120. 120.
    Guttman M, Stewart D, Hussey D, Wilson A, Houle S, Kish S. Influence of l-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology 2001;56:1559–64.PubMedGoogle Scholar
  121. 121.
    Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291:317–24.PubMedGoogle Scholar
  122. 122.
    Page G, Peeters M, Maloteaux JM, Hermans E. Increased dopamine uptake in striatal synaptosomes after treatment of rats with amantadine. Eur J Pharmacol 2000;403:75–80.PubMedGoogle Scholar
  123. 123.
    Gordon I, Weizman R, Rehavi M. Modulatory effect of agents active in the presynaptic dopaminergic system on the striatal dopamine transporter. Eur J Pharmacol 1996;298:27–30.PubMedGoogle Scholar
  124. 124.
    Di Paolo T. Modulation of brain dopamine transmission by sex steroids. Rev Neurosci 1994;5:27–42.PubMedGoogle Scholar
  125. 125.
    Best SE, Sarrel PM, Malison RT, Laruelle M, Zoghbi SS, Baldwin RM, et al. Striatal dopamine transporter availability with [123I]β-CIT SPECT is unrelated to gender or menstrual cycle. Psychopharmacology (Berl) 2005;183:181–9.Google Scholar
  126. 126.
    Gardiner SA, Morrison MF, Mozley PD, Mozley LH, Brensinger C, Bilker W, et al. Pilot study on the effect of estrogen replacement therapy on brain dopamine transporter availability in healthy, postmenopausal women. Am J Geriatr Psychiatry 2004;12:621–30.PubMedGoogle Scholar
  127. 127.
    Collins SL, Gerdes RM, D’Addario C, Izenwasser S. Kappa opioid agonists alter dopamine markers and cocaine-stimulated locomotor activity. Behav Pharmacol 2001;12:237–45.PubMedGoogle Scholar
  128. 128.
    Bergström KA, Jolkkonen J, Kuikka JT. Fentanyl decreases β-CIT binding to the dopamine transporter. Synapse 1998;29:413–5.PubMedGoogle Scholar
  129. 129.
    Izenwasser S, Newman AH, Cox BM, Katz JL. The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter. Eur J Pharmacol 1996;297:9–17.PubMedGoogle Scholar
  130. 130.
    Lomenzo SA, Izenwasser S, Gerdes RM, Katz JL, Kopajtic T, Trudell ML. Synthesis, dopamine and serotonin transporter binding affinities of novel analogues of meperidine. Bioorg Med Chem Lett 1999;9:3273–6.PubMedGoogle Scholar
  131. 131.
    Lomenzo SA, Rhoden JB, Izenwasser S, Wade D, Kopajtic T, Katz JL, et al. Synthesis and biological evaluation of meperidine analogues at monoamine transporters. J Med Chem 2005;48:1336–43.PubMedGoogle Scholar
  132. 132.
    Xiao ZW, Cao CY, Wang ZX, Li JX, Liao HY, Zhang XX. Changes of dopamine transporter function in striatum during acute morphine addiction and its abstinence in rhesus monkey. Chin Med J 2006;119:1802–7.PubMedGoogle Scholar
  133. 133.
    Simantov R. Chronic morphine alters dopamine transporter density in the rat brain: possible role in the mechanism of drug addiction. Neurosci Lett 1993;163:121–4.PubMedGoogle Scholar
  134. 134.
    Kish SJ, Kalasinsky KS, Derkach P, Schmunk GA, Guttman M, Ang L, et al. Striatal dopaminergic and serotonergic markers in human heroin users. Neuropsychopharmacology 2001;24:561–7.PubMedGoogle Scholar
  135. 135.
    Beekman F, van der Have F. The pinhole: gateway to ultra-high-resolution three-dimensional radionuclide imaging. Eur J Nucl Med Mol Imaging 2007;34:151–61.PubMedGoogle Scholar
  136. 136.
    Cherry SR. The 2006 Henry N. Wagner lecture: of mice and men (and positrons)—advances in PET imaging technology. J Nucl Med 2006;47:1735–45.PubMedGoogle Scholar
  137. 137.
    Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N. Ketamine alters the availability of striatal dopamine transporter as measured by [11C]β-CFT and [11C]β-CIT-FE in the monkey brain. Synapse 2001;42:273–80.PubMedGoogle Scholar
  138. 138.
    Harada N, Ohba H, Fukumoto D, Kakiuchi T, Tsukada H. Potential of [18F]β-CFT-FE (2β-carbomethoxy-3β-(4-fluorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter ligand: a PET study in the conscious monkey brain. Synapse 2004;54:37–45.PubMedGoogle Scholar
  139. 139.
    Byas-Smith MG, Li J, Szlam F, Eaton DC, Votaw JR, Denson DD. Isoflurane induces dopamine transporter trafficking into the cell cytoplasm. Synapse 2004;53:68–73.PubMedGoogle Scholar
  140. 140.
    Nishimura M, Sato K. Ketamine stereoselectively inhibits rat dopamine transporter. Neurosci Lett 1999;274:131–4.PubMedGoogle Scholar
  141. 141.
    Riley SC, James C, Gregory D, Dingle H, Cadger M. Patterns of recreational drug use at dance events in Edinburgh, Scotland. Addiction 2001;96:1035–47.PubMedGoogle Scholar
  142. 142.
    Schiffer WK, Logan J, Dewey SL. Positron emission tomography studies of potential mechanisms underlying phencyclidine-induced alterations in striatal dopamine. Neuropsychopharmacology 2003;28:2192–8.PubMedGoogle Scholar
  143. 143.
    Greenblatt DJ. Basic pharmacokinetic principles and their application to psychotropic drugs. J Clin Psychiatry 1993;54:S8–13.Google Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Nuclear Medicine, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.Department of Nuclear MedicineSouthampton University Hospitals TrustSouthamptonUK

Personalised recommendations